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Background and study aims Data from Japanese series show that surface morphology of laterally spreading tumors (LST) in the colon identifies lesions with different incidence and pattern of submucosal invasion. Such data from western countries are scarce. We compared clinical and histological features of LST in a western country and an eastern country, with special interest on mucosal invasiveness of LST, and investigated the effect of clinical factors on invasiveness in both countries. Patients and methods Patients with LST lesions ≥20 mm were included from a multicenter prospective registry in Spain and from a retrospective registry from the National Cancer Center Hospital East, Japan. The primary outcome was the presence of submucosal invasion in LST. The secondary outcome was the presence of high-risk histology, defined as high-grade dysplasia or submucosal invasion. Results We evaluated 1102 patients in Spain and 663 in Japan. Morphological and histological characteristics differed. The prevalence of submucosal invasion in Japan was six-fold the prevalence in Spain (Prevalence Ratio PR = 5.66; 95%CI: 3.96, 8.08), and the prevalence of high-risk histology was 1.5 higher (PR = 1.44; 95%CI: 1.31, 1.58). Compared to the granular homogeneous type and adjusted by clinical features, granular mixed, flat elevated, and pseudo-depressed types were associated with higher odds of submucosal invasion in Japan, whereas only the pseudo-depressed type showed higher risk in Spain. Regarding high-risk histology, both granular mixed and pseudo-depressed were associated with higher odds in Japan, compared with only the granular mixed type in Spain. Conclusion This study reveals differences in location, morphology and invasiveness of LST in an eastern and a western cohort.

O presente trabalho tem como objetivo compreender a dimensão do conhecimento e a visão dos gestores dos mais variados seguimentos sobre a importância da aplicação das práticas de Tecnologia da Informação Verde nas organizações. A metodologia empregada para o desenvolvimento do trabalho foi a analise fenomenológica, que busca a compreensão de um determinado fenômeno interrogado, não se preocupando com explicações e generalizações. Foi estruturado na formulação de uma pergunta central, aplicação de pesquisa qualitativa e análise de dados, que segue os princípios de Merleau-Ponty, sendo; Descrição, Redução e Compreensão. Por meio desta metodologia pôde-se extrair do discurso do sujeito unidades de significado que permitiram o levantamento dos dados necessários à discussão. Os resultados mostram a existência de três categorias de compreensão sobre o assunto, Meio Ambiente, Marca e Superficial, onde cada discurso foi cuidadosamente estudado e qualificado. Concluindo, observa-se que é um tema emergente e abrangente onde suas práticas se mostram cada vez mais imprescindíveis à medida que cresce a dependência da sociedade atual pelo uso de tecnologias. Diante deste cenário é indubitável que novos estudos virão a contribuir para a sustentação da importância da tecnologia verde nas organizações. Palavras-Chave: Tecnologia da informação Verde. Meio Ambiente. Gestores.

Supplementary Figure 1 from Concordant DNA Methylation in Synchronous Colorectal Carcinomas

Epigenetic changes have been proposed as mediators of the field defect in colorectal carcinogenesis, which has implications for risk assessment and cancer prevention. As a test of this hypothesis, we evaluated the methylation status of eight genes (MINT1, 2, 31, MLH1, p16, p14, MGMT, and ESR1), as well as BRAF and KRAS mutations, in 57 multiple colorectal neoplasias (M-CRN) and compared these to 69 solitary colorectal cancers (S-CRC). There were no significant differences in methylation between M-CRNs and S-CRCs except for p14 and MGMT that was significantly higher in M-CRNs than S-CRCs (16.1% versus 9.3%; 26.5% versus 17.3%, respectively; P < 0.05). We found significant (P < 0.05) correlations for MINT1 (r = 0.8), p16 (r = 0.8), MLH1 (r = 0.9), and MGMT (r = 0.6) methylation between tumors pairs of the same site (proximal/proximal and distal/distal). KRAS showed no concordance in mutations. BRAF mutation showed concordance in proximal site pairs but was discordant in different site pairs. Histologically, eight of 10 paired cancers with similar locations were concordant for a cribriform glandular configuration. We conclude that synchronous colorectal tumors of the same site are highly concordant for methylation of multiple genes, BRAF mutations, and a cribriform glandular configuration, all consistent with a patient-specific predisposition to particular subtypes of colorectal cancers. Screening for and secondary prevention of colon cancer should take this fact into account.

Highlights • Study of wetland sediment in the easternmost Asian monsoon affected region. • Sediment on the Konsen Plateau has continuously deposited since ∼4.0 ka. • C/N and C/S ratios suggest environmental changes during the late Holocene. Abstract Wetland soils are among the largest carbon reservoirs in terrestrial ecosystems and are vulnerable to climate change. Here we elucidate the developmental history of a wetland soil located on the Konsen Plateau in Hokkaido, Japan, during the Holocene. Through radiocarbon dating of sediment samples, we revealed that continuous sedimentation persisted over the past 4000 years. This onset of peat sedimentation was simultaneous with those reported in other wetlands in eastern Hokkaido. We hypothesized that cooling associated with the end of climatic optimal may have contributed to peat preservation. Elemental analyses also confirmed the formation of a stable wetland condition during the late Holocene. The C/N ratios were approximately 15–25 throughout the core, indicating that the organic materials in the sediments were steadily derived from terrestrial plants. The C/S ratios of the core varied between 43 and 97, suggesting that the sediments are free from marine influences. Our results provided continuous and stable record of wetland sedimentary environment in eastern Hokkaido over the past 4000 years.

A 62-year-old man was incidentally found to have a pancreatic tumor by CT. He was diagnosed with pancreatic cancer by EUS-FNAB. Gemcitabine(GEM)plus nab-paclitaxel(PTX)was started as neoadjuvant chemotherapy(NAC)for resectable pancreatic cancer. However, after the end of the second course, the tumor grew rapidly and invaded the stomach, so NAC was discontinued, and surgery was performed. The pathological diagnosis was anaplastic ductal carcinoma of the pleomorphic cell type, and the histological response was Grade 1a. Multiple liver metastases appeared during adjuvant chemotherapy with S-1, so GEM plus nab-PTX and modified FOLFIRINOX were administered, but the therapeutic response was poor, the patient died 9 months after surgery. Anaplastic carcinoma has a poor response to chemotherapy and may be included with cancers showing treatment resistance to NAC, as seen in our case. It is necessary to pay attention to anaplastic carcinoma during the course of NAC for pancreatic cancer.

Background and study aims With magnifying narrow-band imaging (M-NBI) of the gastric mucosa, a characteristic demarcation line (DL) is occasionally found in non-cancerous depressed lesions. This DL forms multiple convex shapes along the edge of the epithelia of surrounding mucosa. We have termed this novel finding a multiple convex DL (MCDL). In this study, we clarified the prevalence of an MCDL in depressed gastric lesions detected in patients at high risk for gastric cancer and determined the diagnostic yield necessary to distinguish between cancer and non-cancer. Patients and methods This was a post hoc analysis of a multicenter prospective trial. In total, 362 small (≤ 10 mm) depressed lesions were detected in 1353 patients. Presence or absence of a DL in target lesions was evaluated on M-NBI images. The proportion of MCDLs among lesions with a DL was evaluated. Results Images of 347 lesions (39 cancerous and 308 non-cancerous) were evaluable. A DL was present in 252/347 lesions (73 %). When the cutoff value for the proportion of MCDLs needed to distinguish non-cancer from cancer was set at two-thirds, an MCDL was observed in 86/252 lesions (34 %). In 86 lesions with an MCDL, 83 (97 %) were non-cancerous. The sensitivity, specificity, positive predictive value, and negative predictive value of an MCDL for non-cancerous lesions were 38 %, 91 %, 97 %, and 19 %, respectively. Conclusions Presence of an MCDL had high specificity and positive predictive value for non-cancerous lesions. Evaluating the shape of the DL is useful for differentiation between cancer and non-cancerous lesions.

A "skirt" is a slightly elevated flat lesion with wide pits occasionally observed at the margin of laterally spreading tumors (LSTs). However, the endoscopic treatment outcomes of LSTs with skirts have not been clarified. The aim of this study was to evaluate the endoscopic treatment outcomes of LSTs with skirts.Between February 2006 and March 2014, 996 LSTs were retrospectively examined to assess the clinicopathologic characteristics, procedure time, en bloc resection rate, R0 resection rate, adverse events, and local recurrence rate of endoscopic submucosal dissection (ESD) and of endoscopic resection.Endoscopic treatment was performed in 35 cases of LSTs with skirts (ratio of ESD to endoscopic piecemeal mucosal resection [EPMR], 32:3) and 961 cases of LSTs without skirts (ratio of ESD to EMR to EPMR to polypectomy, 381:275:114:191). LSTs with a skirt were associated with a significantly higher recurrence rate (P .01). In both ESD and EPMR, LSTs with a skirt were associated with a higher recurrence rate when compared with LSTs without a skirt (odds ratio, 12.7; P = .032, and odds ratio, 12.3; P = .061, respectively). Multivariate analysis demonstrated that the presence of the skirt and piecemeal resection were significant predictors of local recurrence.LSTs with skirts had a significantly higher local recurrence rate after endoscopic treatment compared with LSTs without skirts, especially after EPMR. Therefore, ESD should be recommended as an endoscopic treatment for LSTs with skirts to minimize local recurrence.

We developed a lead substances selection approach based on the concept of mixture classification of UN GHS for the purpose of efficient risk assessment of mixtures consisting of multiple components. Lead substances selection methods are being actively developed in Europe, but these methods are predicated on the regulations and information sources available within Europe and are therefore not readily applicable to countries outside Europe. In this study, the features of the GHS-based approach and the risk assessment results for outdoor painting work as a specific utilization example of the GHS-based approach were described. Comparison with the DPD + method and the CCA method proposed in Europe revealed that the GHS-based approach resulted in the selection of the safest lead substances. The GHS method, like the DPD + method, is a classification-based approach. We believe that a classification-based approach based on the GHS method can be an appropriate tool to efficiently implement risk assessment of mixtures for countries outside Europe. Some tools for business operators to conduct the management of chemicals using the GHS classification have been established in Japan. We plan to propose the GHS-based approach as a standardized assessment tool.

// Ayumi Niwa 1, * , Seiya Kuwano 1, * , Hiroyuki Tomita 1 , Keita Kimura 1 , Yukiya Orihara 1 , Tomohiro Kanayama 1 , Kei Noguchi 1 , Kenji Hisamatsu 1 , Takayuki Nakashima 1 , Yuichiro Hatano 1 , Akihiro Hirata 2 , Tatsuhiko Miyazaki 3 , Kazuhiro Kaneko 4 , Takuji Tanaka 5 and Akira Hara 1 1 Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan 2 Division of Animal Experiment, Life Science Research Center, Gifu University, Gifu, Japan 3 Division of Pathology, Gifu University Hospital, Gifu, Japan 4 Department of Gastroenterology, Endoscopy Division, National Cancer Center Hospital East, Kashiwa, Japan 5 Department of Diagnostic Pathology (DDP) and Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, Gifu, Japan * These authors have contributed equally to this work Correspondence to: Hiroyuki Tomita, email: h_tomita@gifu-u.ac.jp Keywords: duodenal neoplasms, beta-catenin Received: October 24, 2016 Accepted: February 27, 2017 Published: April 12, 2017 ABSTRACT Non-ampullary duodenal adenoma with activation of Wnt/β-catenin signalling is common in familial adenomatous polyposis (FAP) patients, whereas sporadic non-ampullary adenoma is uncommon. The adenoma-carcinoma sequence similar to colon cancer is associated with duodenal tumors in FAP, but not always in sporadic tumors. We obtained 37 non-ampullary duodenal tumors, including 25 adenomas and 12 adenocarcinomas, were obtained from biopsies and endoscopic resections. We performed immunohistochemistry for β-catenin, the hallmark of Wnt activation, and aldehyde dehydrogenase 1 (ALDH1), a putative cancer stem cell marker. In non-ampullary lesions, abnormal nuclear localization of β-catenin was observed in 21 (84.0%) of 25 adenomas and 4 (33.3%) of 12 adenocarcinomas. In the proximal duodenum, nuclear β-catenin was less frequent in both adenomas and adenocarcinomas. Gastric duodenal metaplasia (GDM) was observed only in the proximal duodenum. All adenomas with GDM were the gastric foveolar and pyloric gland types, and showed only membranous β-catenin. The intestinal-type adenomas had nuclear β-catenin in the proximal and distal duodenum. ALDH1-positive cells were more frequent in adenocarcinomas than adenomas. Nuclear β-catenin accumulation frequently occurred in ALDH1-positive cells in adenoma, but not in adenocarcinoma. In the non-ampullary proximal duodenum, Wnt/β-catenin pathway activation was more closely associated with adenomas than adenocarcinomas, and while it might cooperate with ALDH1 in adenoma, it does not in adenocarcinoma. The pathogenesis thus may differ between sporadic adenoma and adenocarcinoma of non-ampullary duodenal lesions, especially in the proximal and distal duodenum.

Endoscopic resection has been limited to intestinal-type gastric cancer (cT1a) with a low risk of lymph node metastasis (T1a ≤2 cm, without ulcers). This single-arm confirmatory trial evaluated the efficacy and safety of endoscopic submucosal dissection (ESD) for >2 cm ulcer-negative and ≤3 cm ulcer-positive intestinal-type gastric cancer (cT1a). The eligibility criteria included endoscopically diagnosed cT1a, a single primary intestinal-type gastric adenocarcinoma, an ulcer-negative lesion of any size or a ≤3 cm ulcer-positive lesion, cN0M0, and no prior treatment. If ESD resulted in noncurative resection, surgical resection was added. The primary endpoint was the 5-year overall survival (OS) (planned sample size was 470, with a one-sided alpha level of 2.5%). The threshold 5-year OS was 86.1%. We enrolled 470 early gastric cancer patients [median tumor size, 25 (5–130) mm] from 29 institutions between June 2007 and October 2010. These patients had 152 ulcer-negative lesions (>2 and ≤3 cm), 111 ulcer-negative lesions (>3 cm), and 207 ulcer-positive lesions (≤3 cm). The success rate for en block resection was 99.1% (466/470). Additional gastrectomy was conducted in 131 patients (28%) who did not fulfill the curative resection criteria. The 5-year OS of all patients was 97.0% (95% confidence interval, 95.0–98.2%), which was higher than the threshold 5-year OS (86.1%). The 317 patients who satisfied the curative resection criteria had no recurrence. There were no ESD-related grade 4 adverse events. ESD for early gastric cancers that met the expanded criteria for intestinal-type gastric cancer (cT1a) was acceptable and should be the standard treatment instead of gastrectomy.

AIM To evaluate the clinical impact of surveillance for head and neck (HN) region with narrow band imaging (NBI) in patients with esophageal squamous cell carcinoma (ESCC). METHODS Since 2006, we introduced the surveillance for HN region using NBI for all patients with ESCC before treatment, and each follow-up. The patients with newly diagnosed stage I to III ESCC were enrolled and classified into two groups as follows: Group A (no surveillance for HN region); between 1992 and 2000), and Group B (surveillance for HN region with NBI; between 2006 and 2008). We comparatively evaluated the detection rate of superficial head and neck squamous cell carcinoma (HNSCC), and the serious events due to metachronous advanced HNSCC during the follow-up. RESULTS A total 561 patients (group A: 254, group B: 307) were enrolled. Synchronous superficial HNSCC was detected in 1 patient (0.3%) in group A, and in 12 (3.9%) in group B (P = 0.008). During the follow up period, metachronous HNSCC were detected in 10 patients (3.9%) in group A and in 30 patients (9.8%) in group B (P = 0.008). All metachronous lesions in group B were early stage, and 26 patients underwent local resection, however, 6 of 10 patients (60%) in group A lost their laryngeal function and died with metachronous HNSCC. CONCLUSION Surveillance for the HN region by using NBI endoscopy increase the detection rate of early HNSCC in patients with ESCC, and led to decrease serious events related to advanced metachronous HNSCC.

Endoscopic submucosal dissection is recommended for early gastric cancer with a low risk of lymph node metastasis. When the pathological findings do not meet the curative criteria; then, an additional gastrectomy with lymph node dissection is recommended. However, most cases have neither lymph node metastasis nor a local residual tumor during an additional surgery.This was a single-institutional retrospective cohort study, analyzing 200 patients who underwent an additional gastrectomy after non-curative endoscopic submucosal dissection from January 2005 to October 2015. We reviewed the patients' clinicopathological data and evaluated the predictors for the presence of a residual tumor.Histopathology revealed lymph node metastasis in 15 patients (7.5 %) and a local residual tumor in 23 (11.5 %). A multivariable analysis revealed macroscopic findings (flat/elevated type) (p = 0.011, odds ratio = 4.63), lymphatic invasion (p 0.0001, odds ratio = 14.2), and vascular invasion (p = 0.04, odds ratio = 4.00) to be predictors for lymph node metastasis. A positive vertical margin (p = 0.0027, odds ratio = 3.26) and horizontal margin (p = 0.0008, odds ratio = 5.74) were predictors for a local residual tumor. All cases with lymph node metastasis had lymphovascular invasion with at least one other non-curative factor.The risk of a residual tumor can, therefore, be estimated based on the histopathology of endoscopic submucosal dissection samples. Lymphovascular invasion appears to be a pivotal predictor of lymph node metastasis.

Many clinical studies on narrow-band imaging (NBI) magnifying endoscopy classifications advocated so far in Japan (Sano, Hiroshima, Showa, and Jikei classifications) have reported the usefulness of NBI magnifying endoscopy for qualitative and quantitative diagnosis of colorectal lesions. However, discussions at professional meetings have raised issues such as: (i) the presence of multiple terms for the same or similar findings; (ii) the necessity of including surface patterns in magnifying endoscopic classifications; and (iii) differences in the NBI findings in elevated and superficial lesions. To resolve these problems, the Japan NBI Expert Team (JNET) was constituted with the aim of establishing a universal NBI magnifying endoscopic classification for colorectal tumors (JNET classification) in 2011. Consensus was reached on this classification using the modified Delphi method, and this classification was proposed in June 2014. The JNET classification consists of four categories of vessel and surface pattern (i.e. Types 1, 2A, 2B, and 3). Types 1, 2A, 2B, and 3 are correlated with the histopathological findings of hyperplastic polyp/sessile serrated polyp (SSP), low-grade intramucosal neoplasia, high-grade intramucosal neoplasia/shallow submucosal invasive cancer, and deep submucosal invasive cancer, respectively.

Upon differentiation of cells, remarkable changes in the structures of glycans linked to lipids on cell surface have been observed. Lactosylceramide (Lac-Cer) serves as a common precursor for a series of glycosphingolipids with diverse structures. In the present study, we examined the underlying mechanism for the biosynthesis of Lac-Cer upon differentiation of 3T3-L1 mouse preadipocytes to adipocytes. TLC analysis showed that the amounts of Lac-Cer decrease in 3T3-L1 adipocytes compared to 3T3-L1 preadipocytes. In accordance with this change, the gene expression level of β4-galactosyltransferase (β4GalT) 5, which was identified as Lac-Cer synthase, decreased drastically upon differentiation of 3T3-L1 preadipocytes. The analysis of the transcriptional mechanism of the β4GalT5 gene demonstrated that the core promoter region is identified between nucleotides -299 and -1 relative to the translational start site. During adipocyte differentiation, the expression levels and promoter activities of the β4GalT5 gene decreased dramatically. Since the Specificity protein 1 (Sp1)-binding sites in the promoter region were critical for the promoter activity, it is suggested that Sp1 plays an important role for the expression of the β4GalT5 gene in 3T3-L1 cells. The gene and protein expression of Sp1 decreased significantly upon differentiation of 3T3-L1 preadipocytes. Taken together, the present study suggest that the expression of the β4GalT5 gene decreases through reduced expression of the Sp1 gene and protein upon differentiation of 3T3-L1 peradipocytes to adipocytes, which may lead to the decreased amounts of Lac-Cer in 3T3-L1 adipocytes.

Standard therapy for gastric diffuse large B‐cell lymphoma (DLBCL) is considered to be chemotherapy with or without involved‐field radiation therapy. Although R‐CHOP therapy alone is widely used for DLBCL with gastric lesions (DLBCL‐GL), the outcome and incidence of treatment‐related gastric complications following R‐CHOP are not well known. This study aimed to evaluate the outcome after R‐CHOP therapy in patients with gastric DLBCL including gastric complications and to identify risk factors for the complications. Consecutive patients with newly diagnosed DLBCL‐GL treated with R‐CHOP between 2003 and 2014 were retrospectively evaluated. DLBCL‐GL was defined only when pathologically confirmed in the stomach. Of the 96 patients with DLBCL‐GL, 63 patients were diagnosed with gastric symptoms. Eighty‐eight patients (92%) completed six to eight cycles of R‐CHOP. The complete remission (CR) rate was 86%, and 3‐year and 5‐year overall survival rates were 80% and 73%, respectively. Patients were well stratified according to the Revised International Prognostic Index (R‐IPI). Complication rate was 8% (8/96); seven patients had bleeding and three had stenosis. No patients had gastric perforation. Bleeding occurred during the first cycle of R‐CHOP in five patients (5/7, 71%). Patients with gastric complications had a lower R‐CHOP completion rate (50%, P = 0.001) and a lower CR rate (25%, P

Endoscopic submucosal resection with a ligation device (ESMR-L) is effective for rectal neuroendocrine tumors (NETs); however, its effectiveness for duodenal NETs is unclear. This study evaluated the efficacy and safety of ESMR-L for duodenal NETs. A total of 32 consecutive patients with duodenal NETs were treated in our hospital between December 2010 and August 2015. Among these 32 patients, we retrospectively analyzed the data of all patients who underwent ESMR-L for the treatment of duodenal NETs. ESMR-L was considered for patients in whom (1) the lesion size was ≤10 mm in diameter, (2) the lesion was located within the submucosal layer, and (3) no lymph node metastasis or distant metastasis was detected. Five patients underwent ESMR-L for the treatment of duodenal NETs. The en bloc complete resection rate was 100 %. The median procedure time for ESMR-L was 15 min (range 10–30 min). In all patients, perforation during and after the operation, and intraoperative bleeding were not observed; however, one patient experienced postoperative bleeding. During follow-up, no local recurrence or distant metastasis was noted in any of the patients. ESMR-L is feasible, effective, and safe for duodenal NETs measuring ≤10 mm in diameter that are confined to the submucosal layer without metastasis.

Primary adenocarcinoma arising from heterotopic gastric mucosa (HGM) is rare and the clinicopathological characteristics are not well known. We present two cases of esophageal adenocarcinoma arising from HGM with a review of a case series. Case 1 was a 78-year-old woman who underwent a periodic medical examination without complaining of any symptoms. Preoperative evaluation suggested esophageal adenocarcinoma arising from the HGM. The patient was treated with endoscopic submucosal dissection. Definitive pathological diagnosis confirmed adenocarcinoma arising from the HGM. Case 2 was a 70-year-old man who underwent a medical examination after complaining of dysphagia. Preoperative diagnosis suggested esophageal adenocarcinoma; however, its origin was unclear. The patient was treated with surgical resection. Definitive pathological diagnosis revealed adenocarcinoma arising from the HGM. In this article, the authors report the clinicopathological features of esophageal adenocarcinoma arising from HGM that were collected from a literature review and our cases.

Localization of colorectal tumors during laparoscopic surgery is generally performed by tattooing into the submucosal layer of the colon. However, faint and diffuse tattoos may lead to difficulties in recognizing cancer sites, resulting in inappropriate resection of the colon. We previously demonstrated that yttrium oxide nanoparticles doped with the rare earth ions (ytterbium and erbium) (YNP) showed strong near-infrared (NIR) emission under NIR excitation (1550 nm emission with 980 nm excitation). NIR light can penetrate deep tissues. In this study, we developed an NIR laparoscopy imaging system and demonstrated its use for accurate resection of the colon in swine. The NIR laparoscopy system consisted of an NIR laparoscope, NIR excitation laser diode, and an NIR camera. Endo-clips coated with YNP (NIR clip), silicon rubber including YNP (NIR silicon mass), and YNP solution (NIR ink) were prepared as test NIR markers. We used a swine model to detect an assumed colon cancer site using NIR laparoscopy, followed by laparoscopic resection. The NIR markers were fixed at an assumed cancer site within the colon by endoscopy. An NIR laparoscope was then introduced into the abdominal cavity through a laparoscopy port. NIR emission from the markers in the swine colon was successfully recognized using the NIR laparoscopy imaging system. The position of the markers in the colon could be identified. Accurate resection of the colon was performed successfully by laparoscopic surgery under NIR fluorescence guidance. The presence of the NIR markers within the extirpated colon was confirmed, indicating resection of the appropriate site. NIR laparoscopic surgery is useful for colorectal cancer site recognition and accurate resection using laparoscopic surgery.

Whether proton pump inhibitors (PPIs) relieve heartburn or precordial pain after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to investigate the efficacy of PPI therapy for these symptoms after ER for ESCC. We conducted a multicenter prospective randomized controlled trial among 15 hospitals in Japan. In total, 229 patients with cT1a ESCC were randomly assigned to receive PPI therapy for 5 weeks after ER (the PPI group, n = 115) or follow-up without PPI therapy (the non-PPI group, n = 114). The primary end point was the incidence of gastroesophageal reflux disease (GERD)-like symptoms after ER from a self-reported questionnaire (Frequency Scale for Symptoms of GERD). Secondary end points were ulcer healing rate at 5 weeks, incidence of pain, improvement rate of symptoms in those who started PPI therapy because of GERD-like symptoms in the non-PPI group, and adverse events. No significant difference was observed in the incidence of GERD-like symptoms after ER between the non-PPI and PPI groups (30 % vs 34 %, respectively). No significant differences were observed in the ulcer healing rate at 5 weeks (84 % vs 85 %) and incidence of pain within 1 week (36 % vs 45 %). In nine of ten patients (90 %) who started PPI therapy because of GERD-like symptoms in the non-PPI group, PPI administration relieved GERD-like symptoms. No adverse events related to PPI administration were observed. PPI therapy is not efficacious in reducing symptoms and did not promote healing of ulcers in patients undergoing ER for ESCC.

The magnetic properties of a melt-spun Fe-dilute Cu 60 Ag 35 Fe 5 alloy are examined by X-ray diffraction, magnetic measurements, and transmission electron microscopy (TEM). The X-ray diffraction patterns show that the as-spun and annealed (773 K×36 ks) samples contain Cu and Ag phases and no Fe phases; thus, most Fe atoms are dispersed as clusters. Magnetic measurements indicate that the as-spun and annealed samples exhibit superparamagnetic behavior at 300 K, whereas ferromagnetic and superparamagnetic behaviors coexist at 4.2 K. The magnetic moments of small clusters at 300 K are determined by the nonlinear least squares method as 5148 and 4671 μ B for as-spun and annealed samples, respectively, whereas those at 300 K are experimentally determined as 3500 and 3200 μ B . This decrease in magnetic moments may imply the formation of anti-ferromagnetic coupling by annealing. TEM observation of the melt-spun sample suggests that there are three regions with different compositions: Cu-rich, Ag-rich, and Fe-rich with no precipitation in the matrix. In addition, these regions have obscure interfaces. The magnetic clusters are attributed to the Fe-rich regions.

Background and study aim Magnifying narrow-band imaging (M-NBI) is useful for the accurate diagnosis of early gastric cancer (EGC). However, acquiring skill at M-NBI diagnosis takes substantial effort. An Internet-based e-learning system to teach endoscopic diagnosis of EGC using M-NBI has been developed. This study evaluated its effectiveness. Participants and methods This study was designed as a multicenter randomized controlled trial. We recruited endoscopists as participants from all over Japan. After completing Test 1, which consisted of M-NBI images of 40 gastric lesions, participants were randomly assigned to the e-learning or non-e-learning groups. Only the e-learning group was allowed to access the e-learning system. After the e-learning period, both groups received Test 2. The analysis set was participants who scored Results A total of 395 participants from 77 institutions completed Test 1 (198 in the e-learning group and 197 in the non-e-learning group). After the e-learning period, all 395 completed Test 2. The analysis sets were e-learning group: n = 184; and non-e-learning group: n = 184. The mean Test 1 score was 59.9 % for the e-learning group and 61.7 % for the non-e-learning group. The change in accuracy in Test 2 was significantly higher in the e-learning group than in the non-e-learning group (7.4 points vs. 0.14 points, respectively; P Conclusion This study clearly demonstrated the efficacy of the e-learning system in improving practitioners’ capabilities to diagnose EGC using M-NBI.Trial registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000008569).

This paper presents a new method of wavelength selection combined with principle component analysis (PCA) and a hierarchal method for hyperspectral data analysis. Hyperspectral data analysis is a combination of imaging and spectroscopic technology, and is utilized in several fields. In the medical field, if it is possible to distinguish the region of interest by selecting a feature wavelength without the intervention of manufacturers, spectral application as a surgery support system would be feasible. There are several analysis techniques to extract the features using hyperspectral data; however, many of these methods are premised on using all wavelengths. Considering application to endoscopes and other medical devices and reducing number of wavelengths, these methods are not applicable. PCA is a popular analysis for reducing the number of wavelengths, and has been adapted for extracting general and clear features of specimens. However, such extracted features from the body tend to highlight the features of protein and blood making it difficult to extract the features of cancer or other diseases. This paper proposes a two-type feature extraction method that depends on “difference” and “similarity”. In this method, the PCA and hierarchal classification analysis are combined to merge the clusters based on similarity. The feasibility of the proposed method is verified by applying the method to discriminating the cancer of mouse: colonized cancer tissue after three weeks and colonized cancer tissue after one week. The results show that the proposed method can extract the two-type feature. The proposed method is had an accuracy of 75.9% in reducing the number of wavelength bands from 256 to 8 for mature cancer in mice. Although less accurate than using all wavelength bands, the eight wavelength bands are distinguished using a simplified convolutional neural network model with an accuracy of 75.9%. The proposed method is able to select the feature wavelength bands for the target. As the learning model for improving the accuracy advances beyond the simple model and the new feature is extracted in the selected wavelength bands, the method is applied to a diagnosis supporting system for endoscopic surgery and more.

Narrow-band imaging (NBI) has been reported to be useful for detecting superficial-type esophageal or head and neck squamous cell carcinoma (SCC), and in the present study we have used NBI to detect non-carcinomatous lesions, such as basal cell hyperplasia (BCH) accompanied by microvascular irregularities; these non-carcinomatous lesions were pathologically discriminated from squamous cell carcinoma of the pharynx. The aim of the present study was to clarify the endoscopic characteristics of BCH that contribute to the discrimination of superficial-type head and neck SCC (HNSCC). We examined the key endoscopic findings capable of distinguishing BCH from SCC using 26 BCH and 37 superficial-type SCC of the pharynx that had been pathologically diagnosed at our institution between January 2008 and July 2012. The clinicopathological factors were also compared. The size of the BCH lesions was significantly smaller (P < 0.001), and their intervascular transparency was more clearly observed (P < 0.001). Intra-epithelial papillary capillary loop (IPCL) shapes were less variable and monotonous (P < 0.001), and the distribution of the IPCL was more regular with an interval comparable to that of SCC (P < 0.001), although no significant differences in the sharpness of the lesion border, dilatation of IPCL and tortuosity of the IPCL were seen between the BCH and SCC lesions. This study revealed that BCH was an independent entity in terms of not only pathological findings, but also endoscopic findings observed using NBI, such as the regular distribution of IPCL and the preserved intervascular transparency.

Background and study aims: Endoscopic submucosal dissection (ESD) is more difficult and has a higher rate of complications, such as perforation and bleeding, compared with conventional endoscopic resection. The aim of this study was to evaluate the feasibility of a new scissors-type electrosurgical knife for ESD, which was developed for improved durability and ease of use. Materials and methods: Initial ex vivo experiments and subsequent ESD procedures in live pigs were carried out. A human feasibility study was then performed in patients with early esophageal or gastric cancer. The primary end point was serious adverse events (SAE) related to ESD. Results: In the ex vivo and live animal models, no mechanical errors occurred and only minor damage to surrounding tissue was observed. Four patients were enrolled in the human feasibility study; all ESD procedures were completed with a mean procedure time of 31 minutes. All specimens were resected completely without any SAEs. The device worked smoothly, with no electrical problems noted. Conclusion: ESD using a novel scissors-type knife for early esophageal or gastric cancer is feasible. Clinical trial registration: UMIN000004941.

Patients with submucosal invasive colorectal cancer (SM-CRC) treated with endoscopic resection who are at low risk of lymph node metastasis and local recurrence may be followed up with observation alone, while additional surgery is recommended for those with high risk features. However, the long-term outcomes that these strategies offer are still unclear. The objective of our study was to retrospectively evaluate the long-term outcomes of patients with SM-CRC managed with endoscopic resection.We retrospectively analyzed all patients with SM-CRC treated by endoscopic resection at six institutions between 2000 and 2007. SM-CRCs with (i) negative vertical margin, (ii) well or moderately differentiated adenocarcinoma, (iii) absence of lymphovascular invasion, and (iv) invasion depth1000 µm were classified as low risk. Patients with SM-CRCs without these characteristics were classified as high risk. Outcomes were assessed by 5-year recurrence-free survival (RFS) and recurrence rate.During the study period, 428 patients with SM-CRC (low risk, 126; high risk, 302) who underwent endoscopic resection as their first treatment were enrolled (median follow-up 61 months). Among the 120 patients with low risk features treated by endoscopic resection alone, the 5-year RFS and recurrence rates were 98 % and 0.8 %, respectively. Of the 302 patients with high risk features, 196 underwent additional surgery and 106 were managed with endoscopic resection alone. For those who underwent additional surgery, the 5-year RFS and recurrence rates were 97 % and 3.6 %, respectively. Among the 106 patients managed with endoscopic resection alone, RFS and recurrence rates were 89 % (P0.05 vs. low risk patients treated by endoscopic resection alone) and 6.6 % (P0.05), respectively.Endoscopic resection alone is adequate for the management of patients with SM-CRC and low risk features. However, in those patients with SM-CRC and high risk features, surgery should be considered in addition to endoscopic resection.

Little is known about the long-term outcomes of patients with submucosal invasive colorectal cancer who undergo endoscopic or surgical resection. We performed a retrospective analysis of long-term outcomes of patients treated for submucosal colon and rectal cancer.We collected data on 549 patients with submucosal colon cancer and 209 patients with submucosal rectal cancer who underwent endoscopic or surgical resection at 6 institutions over a median follow-up period of 60.5 months. Patients were classified into one of 3 groups: low-risk patients undergoing only endoscopic resection (group A), high-risk patients undergoing only endoscopic resection (group B), and high-risk patients undergoing surgical resection that included lymph node dissection (group C). We assessed recurrence rates, 5-year disease-free survival, and 5-year overall survival. Cox regression analysis was used to compare recurrences.The rates of recurrence, disease-free survival, and overall survival in group A for submucosal colon and rectal cancer were 0% versus 6.3% (P.05), 96% versus 90%, and 96% versus 89%, respectively. For group B, these values were 1.4% versus 16.2% (P.01), 96% versus 77% (P.01), and 98% versus 96%, respectively; local recurrence was observed in 5 patients (one with submucosal colon cancer and 4 with submucosal rectal cancer). Tumor location was the only factor that contributed significantly to disease recurrence and death (hazard ratio, 6.73; P = .045). For group C, these values were 1.9% versus 4.5%, 97% versus 95%, and 99% versus 97%, respectively.The risk for local recurrence was significantly higher in high-risk patients with submucosal rectal cancer than in patients with submucosal colon cancer when treated with only endoscopic resection. The addition of surgery is therefore recommended for patients with submucosal rectal cancer with pathologic features indicating a high risk of tumor progression; University Hospital Medical Network Clinical Trials Registry, Number: UMIN 000008635.

Aldehyde dehydrogenase (ALDH) is overexpressed in some subpopulations of stem cells and cancer cells. We have designed and synthesized the first selective fluorescent probe for class 3 ALDH (ALDH3A1). This probe enabled the visualization of ALDH3A1-positive cells by fluorescence microscopy as well as flow-cytometric isolation of ALDH3A1-positive viable cells from a human Caucasian esophageal squamous cell line (OE21) that heterogeneously expresses ALDH3A1.

Background and Aims Biodegradable stents are reportedly effective for refractory benign esophageal strictures; however, little is known about their use in patients with refractory stricture after endoscopic submucosal dissection (ESD) or chemoradiotherapy (CRT) for esophageal cancer. This study aimed to evaluate the effectiveness of biodegradable stents for these patients. Methods Patients with refractory benign esophageal stricture with a dysphagia score (DS) of 2 or worse and for whom the passage of a standard size endoscope was not possible were eligible. The primary endpoint was the proportion of those who improved their DSs (% DS improved) at 12 weeks after stent placement, and the secondary endpoints were the proportion of those who improved their DSs at 24 weeks, dysphagia-free survival (DFS), and adverse events. Results Eighteen patients (men:women, 15:3; median age, 72 years; range, 53-80) were enrolled. Twelve patients improved their DS at 12 weeks (% DS improved, 66.7%; 90% CI, 44.6%-84.4%). Also, 8 of 11 patients (72.7%) after esophagectomy, 4 of 6 patients (66.7%) after ESD, and 3 of 4 patients (75%) after CRT improved at 12 weeks. Three patients who were treated with esophagectomy maintained their DS improvement at 24 weeks (% DS improved, 16.7%; 95% CI, 3.6%-41.4%). The median DFS was 14.1 weeks (95% CI, 13.0-19.0). One patient who had ESD and CRT developed an esophagobronchial fistula 3 months after stent placement. Conclusions Biodegradable stents are effective and tolerable for refractory benign esophageal strictures after treatment for esophageal cancer; however, long-term efficacy was limited, especially after ESD or CRT. (Clinical trial registration number: UMIN000008054.)

Background: Esophageal squamous cell carcinoma (ESCC) is often synchronously accompanied by pharyngeal squamous cell carcinoma (PSCC). However, treatment strategies for these synchronous cancers have not been established. Aim: To evaluate retrospectively the effects of both chemoradiotherapy (CRT) targeted for invasive ESCC on synchronous superficial PSCC and additional endoscopic resection (ER) for PSCC. Patients and Methods: Screening endoscopy in the pharynx was performed in newly diagnosed ESCC patients. CRT combined with 5-fluorouracil (5-FU) and cisplatin (CDDP) was administered to all patients. The effect on superficial PSCC was only evaluated for 5-FU-CDDP chemotherapy that excluded the pharynx from the radiation field. When PSCC was remnant or recurrent in patients evaluated at complete response (CR) of ESCC, ER was performed on the PSCC. Results: Fourteen cases of superficial PSCC (4.0%) were detected in 348 ESCC patients. Three PSCC reached CR in 8 ESCC-CR patients, while all 3 lesions recurred. No treatment response was found in the remaining 11 PSCC. As a second treatment, ER for 8 PSCC was completed in the 8 ESCC-CR patients, with one complication due to pneumonia. Conclusions: Standard 5-FU-CDDP CRT targeted for invasive ESCC did not demonstrate a sufficient efficacy for superficial PSCC, while ER even for PSCC after chemotherapy was curative.

Concurrent chemoradiotherapy with 5-fluorouracil plus mitomycin C has been established as a standard therapy for non-metastatic anal squamous cell carcinoma in the West. However, there have been few reports of chemoradiotherapy for anal squamous cell carcinoma in Japan. We retrospectively investigated seven consecutive anal squamous cell carcinoma patients who were treated with concurrent chemoradiotherapy consisting of 5-fluorouracil plus mitomycin C with a total irradiation of 59.4 Gy. The patients consisted of two males and five females. Clinical stages II/IIIA/IIIB accounted for four, one and two patients, respectively. Full-dose irradiation was completed in all patients. Median relative dose intensities of 5-fluorouracil and mitomycin C were both 99%. All patients achieved complete response. At a median follow-up of 37.5 months, one patient experienced local recurrence. The most common grade 3/4 acute toxicities were dermatitis in 100% and anal pain in 71%. There was no treatment-related death. Concurrent chemoradiotherapy appears to be tolerable and effective in Japanese patients with anal squamous cell carcinoma.

Local failure at the primary site is a major problem after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC). Salvage surgery is the only treatment option with curative intent, but it is associated with high morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of salvage photodynamic therapy (PDT) after CRT. Patients with histologically proven local failure limited to the submucosal layer, and without any metastasis after definitive CRT (≥50 Gy) for ESCC were enrolled in the study. PDT began with intravenous administration of 2 mg/kg of porfimer sodium followed 48-72 hr later by excimer dye laser irradiation with a fluence of 75 J/cm2. The primary endpoint was a complete response (CR) to treatment with PDT, and the secondary endpoints were toxicity related to PDT, progression-free survival (PFS) and overall survival (OS). Twenty-five patients were enrolled in the study. A CR was attained in 19 of 25 patients treated with PDT (CR rate, 76%; 95% CI, 55-91%). One treatment-related death (4%) caused by gastrointestinal hemorrhage at the irradiated site occurred 33 days after PDT. No adverse events greater than grade 3 were related to PDT in the other patients. After a median follow-up of 48 months after PDT, the PFS and OS at 3 years were 40% (95% CI, 21-59%) and 38% (95% CI, 17-60%), respectively. PDT is a potentially curative and tolerable salvage treatment after CRT for carefully selected patients with local failure without any metastasis.

The occurrence of lung cancer is associated with smoking, which exposes smokers to a series of carcinogenic chemicals. CYP (cytochrome P450) usually metabolizes carcinogens to their inactive derivatives, but occasionally convert the chemicals to more potent carcinogens. In addition to the metabolism of carcinogenic compounds, CYP also participates in the activation and/or inactivation of anti-carcinogenic agents, suggesting that the local CYP expression in lung cancer and surrounding tissues could be an important determinant of efficacy of anticancer drugs. Furthermore, CYP19 (aromatase), estrogen synthase P450, expressed in more than 80 percent of non-small cell lung cancers. It suggests an association between estrogens and cancer development, which makes aromatase an attractive therapeutic target for the treatment of lung cancer. 1alpha,25-Dihydroxyvitamin D3 has an inhibitory effect on the proliferation of cancer tissues, and is converted to its inactive 24-hydroxylated derivatives by CYP24, which is frequently expressed in lung cancer tissues. Therefore, understanding the CYP expression in tumor tissues is important in developing better therapies for lung cancer, and may lead us to standardized, tailor-made therapies for individuals.

胆管癌が急性膵炎の原因となることはまれである．今回，急性膵炎で発症した下部胆管癌の1例を経験したので報告する．症例は65歳の女性で，急性膵炎を発症した．膵炎は保存的治療で軽快するものの，食事の再開で再燃を繰り返した．ERCPでは膵頭部主膵管と下部胆管とに狭窄を認めた．副乳頭からの造影剤の排出を認めなかった．CTでは膵体尾部に主膵管拡張と仮性嚢胞とを認めたが，膵頭部に腫瘤を認めなかった．以上より，主膵管，下部胆管の狭窄を伴う難治性の特発性膵炎と診断された．保存的に治癒が見込めず，小膵管癌による膵炎も否定できないため，膵頭十二指腸切除を施行した．病理組織学的検査で，主膵管浸潤を伴う下部胆管癌（2.4×2.0cm，深達度ss，pPanc2）と診断された．十二指腸主乳頭には異常を認めなかった．以上より，自験例における急性膵炎の原因は，下部胆管癌の主膵管浸潤による膵管内圧上昇と考えられた．

Objective: To retrospectively assess the efficacy and safety of palliative chemoradiotherapy in Stage IVB esophageal cancer patients with dysphagia due to the primary lesion. Methods: Forty patients with dysphagia caused by metastatic esophageal cancer, which had been treated between January 2004 and June 2009, were retrospectively investigated. The treatment consisted of two courses of chemotherapy (5-fluorouracil and cisplatin) and concurrent irradiation of 40 Gy in 20 fractions to the esophageal primary tumor. The grade of dysphagia was evaluated; nutrition-support-free survival was evaluated using the status of nutritional support of patients. Response to treatment, overall survival, progression-free survival and toxicities were also evaluated. Results: Dysphagia score improved in 75% of the patients. Seventeen of the 20 patients (85%) who had required nutritional support at baseline improved their oral intake to no longer need the support, in a median time of 43 days. The median nutrition-support-free survival was 301 days in the 20 patients who had had adequate oral intake before the treatment. Disease control rate of the primary lesion was 95%, including 12 patients (30%) who achieved a complete response. The overall response rate was 55%. The median survival was 308 days, and the 1-year-survival rate was 45.0%. The median progression-free survival was 139 days. Toxicities were generally well tolerated. Major toxicities (Grade 3 or 4) involved hemoglobin (23%), leukocytes (15%), neutrophils (20%), anorexia (10%), nausea (3%), esophageal perforation (5%) and febrile neutropenia (3%). Two patients (5%) died within 30 days of terminating radiotherapy. Conclusions: Palliative chemoradiotherapy using 5-fluorouracil plus cisplatin combined with concurrent 40 Gy irradiation effectively improved the symptom of dysphagia in Stage IVB esophageal cancer with acceptable toxicity and favorable survival.

Background: We aimed to compare the sensitive and quality-controlled KRAS testing with direct sequencing and to assess the impact on decision making of treatment. Patients and methods: We analysed genomic DNA isolated from macrodissected formalin-fixed paraffin-embedded specimens by direct sequencing and an amplification refractory mutation system–Scorpion assay (ARMS/S) method. Cetuximab was administered to patients identified as having wild-type (WT) KRAS using direct sequencing. Therapeutic effects were evaluated according to their KRAS status as determined by ARMS/S. Results: Among the 159 patients, the overall mutation rate was determined to be 37.0% by direct sequencing and 44.0% by ARMS/S. For the patients diagnosed as WT by direct sequencing and treated with cetuximab (n=47), a response rate of 16.0% was observed for 38 ARMS/S WT patients, whereas 9 ARMS/S mutant (MUT) patients failed to respond. The ARMS/S WT patients showed significant improvement in progression-free survival (PFS) and overall survival (OS) compared with ARMS/S MUT patients (PFS median 5.0 vs 1.7 months, hazards ratio (HR)=0.29, P=0.001; OS median 12.1 vs 3.8 months, HR=0.26, P=0.001). Conclusion: Sensitive and quality-controlled KRAS testing may provide improved predictive power to determine the efficacy of anti-epidermal growth factor antibodies.